LncRNAs signatures associated with cuproptosis predict the prognosis of endometrial cancer

Background: Endometrial cancer (UCEC) is the sixth most common cancer in women, and although surgery can provide a good prognosis for early-stage patients, the 5-year overall survival rate for women with metastatic disease is as low as 16%. Long non-coding RNAs (LncRNAs) are thought to play an impor...

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Main Authors: Shiyuan Qi, Huiyan Feng, Xiaomao Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2023.1120089/full
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author Shiyuan Qi
Huiyan Feng
Xiaomao Li
author_facet Shiyuan Qi
Huiyan Feng
Xiaomao Li
author_sort Shiyuan Qi
collection DOAJ
description Background: Endometrial cancer (UCEC) is the sixth most common cancer in women, and although surgery can provide a good prognosis for early-stage patients, the 5-year overall survival rate for women with metastatic disease is as low as 16%. Long non-coding RNAs (LncRNAs) are thought to play an important role in tumor progression. Cuproptosis is a recently discovered form of cell death in which copper binds directly to the lipoacylated component of the tricarboxylic acid (TCA) cycle. The aggregation of these copper-bound listed mitochondrial proteins and the loss of Fe-S cluster proteins trigger proteotoxic stress, which leads to cell death. Therefore, the aim of this work was to investigate the role of Cuproptosis-related LncRNAs signaling in clinical prognostic prediction and immunotherapy, as well as the relationship between tumor mutation burden.Methods: Genomic, clinical and mutational data of endometrial cancer patients were presented in the TCGA database, and cuproptosis-related genes obtained from related studies. Coexpression analysis and Cox regression analysis were used to construct prognostic features. Patients were divided into high risk group and low risk group, and then ROC, survival rate, risk curve, principal component analysis, independent prognostic analysis and clinical subgroup model validation were performed to observe the prognostic value of characteristics. Subsequently, the GO and genomic KEGG enrichment and immune-related functions of LncRNAs as well as the tumor mutation burden were analyzed.Results: In 548 UCEC case data, we identified five associated LncRNAs co-expressed with cuproptosis genes, and we found that high-risk patients had poorer overall survival (OS), progression-free survival (PFS), and higher mortality. Independent prognostic analysis, ROC showed that the LncRNAs associated with cuproptosis could accurately predict the prognosis of patients. Enrichment analysis revealed that the biological functions of LncRNAs were related to tumorigenesis. We also discovered suppression of immune-related functions in high-risk patients with oncogene mutations, higher tumor mutation burden in low-risk patients, and longer overall survival in patients with higher tumor mutation burden.Conclusion: The identification of five LncRNAs associated with cuproptosis can accurately predict the prognosis of patients with endometrial cancer, and may provide a new perspective for clinical application and immunotherapy.
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spelling doaj.art-535cf300bcd740ada1387105a717faae2023-04-12T05:54:14ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-04-011410.3389/fgene.2023.11200891120089LncRNAs signatures associated with cuproptosis predict the prognosis of endometrial cancerShiyuan QiHuiyan FengXiaomao LiBackground: Endometrial cancer (UCEC) is the sixth most common cancer in women, and although surgery can provide a good prognosis for early-stage patients, the 5-year overall survival rate for women with metastatic disease is as low as 16%. Long non-coding RNAs (LncRNAs) are thought to play an important role in tumor progression. Cuproptosis is a recently discovered form of cell death in which copper binds directly to the lipoacylated component of the tricarboxylic acid (TCA) cycle. The aggregation of these copper-bound listed mitochondrial proteins and the loss of Fe-S cluster proteins trigger proteotoxic stress, which leads to cell death. Therefore, the aim of this work was to investigate the role of Cuproptosis-related LncRNAs signaling in clinical prognostic prediction and immunotherapy, as well as the relationship between tumor mutation burden.Methods: Genomic, clinical and mutational data of endometrial cancer patients were presented in the TCGA database, and cuproptosis-related genes obtained from related studies. Coexpression analysis and Cox regression analysis were used to construct prognostic features. Patients were divided into high risk group and low risk group, and then ROC, survival rate, risk curve, principal component analysis, independent prognostic analysis and clinical subgroup model validation were performed to observe the prognostic value of characteristics. Subsequently, the GO and genomic KEGG enrichment and immune-related functions of LncRNAs as well as the tumor mutation burden were analyzed.Results: In 548 UCEC case data, we identified five associated LncRNAs co-expressed with cuproptosis genes, and we found that high-risk patients had poorer overall survival (OS), progression-free survival (PFS), and higher mortality. Independent prognostic analysis, ROC showed that the LncRNAs associated with cuproptosis could accurately predict the prognosis of patients. Enrichment analysis revealed that the biological functions of LncRNAs were related to tumorigenesis. We also discovered suppression of immune-related functions in high-risk patients with oncogene mutations, higher tumor mutation burden in low-risk patients, and longer overall survival in patients with higher tumor mutation burden.Conclusion: The identification of five LncRNAs associated with cuproptosis can accurately predict the prognosis of patients with endometrial cancer, and may provide a new perspective for clinical application and immunotherapy.https://www.frontiersin.org/articles/10.3389/fgene.2023.1120089/fullcuproptosisLncRNAsendometrial cancertargeted therapyprognosis
spellingShingle Shiyuan Qi
Huiyan Feng
Xiaomao Li
LncRNAs signatures associated with cuproptosis predict the prognosis of endometrial cancer
Frontiers in Genetics
cuproptosis
LncRNAs
endometrial cancer
targeted therapy
prognosis
title LncRNAs signatures associated with cuproptosis predict the prognosis of endometrial cancer
title_full LncRNAs signatures associated with cuproptosis predict the prognosis of endometrial cancer
title_fullStr LncRNAs signatures associated with cuproptosis predict the prognosis of endometrial cancer
title_full_unstemmed LncRNAs signatures associated with cuproptosis predict the prognosis of endometrial cancer
title_short LncRNAs signatures associated with cuproptosis predict the prognosis of endometrial cancer
title_sort lncrnas signatures associated with cuproptosis predict the prognosis of endometrial cancer
topic cuproptosis
LncRNAs
endometrial cancer
targeted therapy
prognosis
url https://www.frontiersin.org/articles/10.3389/fgene.2023.1120089/full
work_keys_str_mv AT shiyuanqi lncrnassignaturesassociatedwithcuproptosispredicttheprognosisofendometrialcancer
AT huiyanfeng lncrnassignaturesassociatedwithcuproptosispredicttheprognosisofendometrialcancer
AT xiaomaoli lncrnassignaturesassociatedwithcuproptosispredicttheprognosisofendometrialcancer